Rectal Cancer, Liver Metastasis, Lung Metastasis
Conditions
Keywords
Short course radiotherapy, Modified FOLFOX6, Delayed surgery, Rectal cancer, Synchronous metastasis, Liver metastasis, Lung metastasis
Brief summary
Radical treatment of primary rectal cancer with synchronous distant metastases includes surgical resection of primary and metastatic lesion. However, primary rectal cancer in case of metastasized disease are often locally advanced disease and need downsizing before surgery. It is reported that pelvic recurrence rates and distant metastasis rates outside liver are 30\ 35% and 60%, respectively. Therefore, combined treatment with radiotherapy and chemotherapy is used. However, the sequence of treatment modalities is not yet definitely established and preoperative chemoradiotherapy and surgical resection is accepted as an option of treatment. Conventional long course chemoradiotherapy delays administration of full-dose chemotherapy, and metastatic lesion can be progressed during chemoradiotherapy. In present study, we evaluate the efficacy of short course radiotherapy (SCRT) followed by full-dose chemotherapy with delayed surgical resection of the primary tumor and metastases.
Interventions
RADIATIONShort Course Radiotherapy
Radiotherapy to tumor and draining lymph node with 25 Gy in 5 fractions within 5 working days
DRUGChemotherapy
* Oxaliplatin 85 mg/m2 IV over 2 hrs on Day 1 * Irinotecan 180 mg/m2 IV over 30-90 mins on Day 1 * Leucovorin 400 mg/m2 IV over 2 hrs on Day 1 and 2 * 5-fluorouracil bolus 400 mg/m2 IV push on Day 1 and 2 (or 5-fluorouracil infusion 600 mg/m2 IV continuous infusion over 22 hrs). * Bevacizumab 5 mg/kg IV over 90 mins on Day 1 * Cetuximab (only for patients with K-ras wild type and positive EGFR mutation) 400 mg/m2 IV over 2 hrs on Day 1, and 250 mg/m2 IV over 1 hr on Day 8, 15, 22, 29, and 36. * FOLFOX or FOLFIRI (+-Bevacizumab ) repeats every 14 days for up to 3 courses. Cetuximab repeats every week for up to 6 courses * Postoperative FOLFOX or FOLFIRI (+-Bevacizumab or Cetuximab) for up to 9 cycles (total 12 cycles)
PROCEDUREDelayed Surgery
If primary tumor and metastases is resectable after FOLFOX or FOLFIRI (+-Bevacizumab or Cetuximab) of 3 cycles, patients have surgical resection (and/or radiofrequency ablation to metastases).
Sponsors
Kyung Hee University Hospital at Gangdong
Gachon University Gil Medical Center
Catholic University of Korea, Yeouido St. Mary's Hospital
Pusan National University Yangsan Hospital
Gangnam Severance Hospital
Severance Hospital
Wonju Severance Christian Hospital
Chungnam National University Hospital
Dongtan Sacred Heart Hospital
The Koreran Society of Coloproctology
The Catholic University of Korea
Korea Cancer Center Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed adenocarcinoma of rectum * Lower margin of tumor within 12 cm from anal verge * Clinically locally advanced (T3-4 or N1-2) disease * Potentially resectable and synchronous distant metastases in liver and/or lung. The resectability of metastatic lesions is determined by size, number, location, general condition, liver function, and lung function. * Over 18 years * Eastern Cooperative Oncology Group performance status 0-2 * Proper organ function (Hemoglobin ≥ 10 g/dl, Absolute neutrophil count (ANC) ≥ 1,500/mm3, Platelet ≥ 100,000/mm3, Creatinine ≤ 1.5 mg/dl, Clearance of creatinine \>50 ml/min using Cockcroft-Gault formula, Bilirubin ≤ 1.5 x upper limit of normal (ULN), Liver enzyme (Aspartate aminotransferase/Alanine transaminase/Alkaline phosphatase) ≤ 2.5 x ULN) * Subject who should sign on the informed consent form before participate the trial.
Exclusion criteria
* Metastases in other organ except liver or lung * History of other type of malignancies within 3 years other than non-melanoma of the skin or carcinoma in situ of cervix * Hereditary colorectal cancer (FAP, HNPCC, and etc) * Bowel obstruction or impending bowel obstruction * Uncontrolled severe illness, unsuitable to chemoradiotherapy (within 6 months, myocardial infarct, unstable angina, heart failure, uncontrolled arrhythmia, uncontrolled epilepsy, central nervous system disease, psychological disorder, and etc) * Subject pregnant or breast feeding, or incapable of appropriate contraception * Unresected synchronous colorectal cancer * History of prior pelvic radiotherapy * History of prior chemotherapy for colorectal cancer * Great surgery within 4 week before study enrollment * Participant in other trial within 4 week before study enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| R0 resection rate | Expected average of 12 weeks (after resection) | R0 resection rate of primary and metastatic lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival rate | 2 years | From the first date of radiotherapy to the date of death or last follow-up |
| Progression free survival rate | 2 years | From the first date of radiotherapy to the date of first failure or last follow-up |
| Tumor regression grade | Just after resection & pathologic report | Tumor regression grade of primary lesion |
| Toxicity | 1 year | Adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
Countries
South Korea
Contacts
Primary ContactSun Mi Moon, MD, PhD
Backup ContactWon Il Jang, MD, MS
Outcome results
None listed